Redefining the modern paradigm of vasopressor therapy for vasodilatory shock.

Vasodilatory shock remains a leading cause of morbidity and mortality in the intensive care unit. Vasopressors are the cornerstone of treatment when vasodilatory shock persists despite adequate fluid resuscitation, yet their effects on organ-specific blood flow, perfusion, and oxygenation are complex and may contribute to harm. This review summarises the extensive contributions of Professor Rinaldo Bellomo to advancing our knowledge of vasopressor therapy in clinical practice. Central to his work was the concept of personalised haemodynamic targets, introduced through the concept of "mean perfusion pressure deficit", which linked premorbid perfusion pressure to outcomes and challenged the universal application of a mean arterial pressure threshold of ≥65 mmHg. In collaboration with Professor Clive May, Bellomo established a chronically instrumented large animal model of hyperdynamic sepsis, yielding fundamental insights into the discordance between the macrocirculation and microcirculation, the vulnerability of the renal medulla to hypoxia, and the mechanisms of septic acute kidney injury. This model enabled direct comparison of vasopressor drugs in both healthy animals and during septic shock, demonstrating their heterogeneous effects on global and regional blood flow, perfusion, and tissue oxygenation. Knowledge translation to the bedside was achieved through the conduct of pivotal clinical trials, from early studies refuting the utility of "renal-dose dopamine" to landmark contributions to the ATHOS (angiotensin II treatment of high-ouput shock) program, which established angiotensin II as a novel vasopressor in refractory vasodilatory shock. Collectively, Bellomo's work has transformed vasopressor therapy from empirical convention towards individualised practice, and it continues to inform clinical investigation and guideline development.